Pathogenesis of Henoch-Schönlein purpura nephritis

The severity of renal involvement is the major factor determining the long-term outcome of children with Henoch-Schönlein purpura (HSP) nephritis (HSPN). Approximately 40% children with HSP develop nephritis, usually within 4 to 6 weeks after the initial onset of the typical purpuric rashes. Although the pathogenetic mechanisms are still not fully delineated, several studies suggest that galactose-deficient IgA1 (Gd-IgA1) is recognized by anti-glycan antibodies, leading to the formation of the circulating immune complexes and their mesangial deposition that induce renal injury in HSPN

U-bend shaped turbine blade cooling passage optimization

The U-bend duct which turns flow through 180° is encountered in many engineering applications in mechanical and aerospace systems. One important example is in modern turbine blade cooling systems and, partly for this reason, the U-bend has been the subject of many fluid dynamic and heat transfer investigations. The bend flow combines many complex fluid dynamic phenomena and most of the investigations have focused on understanding of the flow physics or improving the accuracy of numerical simulations. However, reports of research into shape optimization of the U-bend are relatively sparse. The main purpose of the present investigation was to focus on finding a 3-D U-bend configuration with minimum pressure loss. The DOE (Design of Experiment) technique and surrogate design space model have been successfully applied by the authors, instead of direct optimization, to reduce computational time. Copyright © 2008 by the author(s)

The terminal nucleotide of the Mu genome controls catalysis of DNA strand transfer

Members of the transposase/retroviral-integrase superfamily use a single active site to perform at least two reactions during transposition of a DNA transposon or a retroviral cDNA. They hydrolyze a DNA sequence at the end of the mobile DNA and then join this DNA end to a target DNA (a reaction called DNA strand transfer). Critical to understanding the mechanism of recombination is elucidating how these distinct reactions are orchestrated by the same active site. Here we find that DNA substrates terminating in a dideoxynucleotide allow Mu transposase to hydrolyze a target DNA, combining aspects of both natural reactions. Analyses of the sequence preferences for target hydrolysis and of the structure of the cleaved product indicate that this reaction is promoted by the active site in the conformation that normally promotes DNA strand transfer. Dissecting the DNA requirements for target hydrolysis reveals that the ribose of the last nucleotide of the Mu DNA activates transposase's catalytic potential, even when this residue is not a direct chemical participant. These findings provide insight into the molecular mechanism insuring that DNA strand transfer ordinarily occurs rather than inappropriate DNA cleavage. The required presence of the terminal nucleotide in the transposase active site creates a great advantage for the attached 3′OH to serve as nucleophile